TY  - JOUR
A1  - Schmidt, Sebastian
A1  - Holzgrabe, Ulrike
T1  - Method development, optimization, and validation of the separation of ketamine enantiomers by capillary electrophoresis using design of experiments
JF  - Chromatographia
N2  - Capillary electrophoresis was chosen as cost-effective and robust method to separate ketamine enantiomers. For the method development, first different native and modified cyclodextrins were tested. The most promising chiral selector was α-cyclodextrin. A design of experiments (DoE) was carried out, which started with the screening of relevant factors. Based on these results, the method was optimized according to the significant factors (buffer, cyclodextrin concentration, pH value, voltage, temperature) of the screening based on the response resolution and migration time of the later migrating enantiomer. The optimized conditions consisted of a background electrolyte with 275 mM TRIS, adjusted with 85% phosphoric acid to a pH of 2.50, and 50 mM α-cyclodextrin, at a temperature of 15 °C, an applied voltage of 30 kV and an injection pressure of 1.0 psi for 10 s. A fused-silica capillary with a total length of 70 cm and an effective length to the detector of 60 cm was used. The method was validated according to ICH guideline Q2 R(1). The limit of quantification was 3.51 µg mL\(^{−1}\) for S-ketamine and 3.98 µg mL\(^{−1}\)for R-ketamine. The method showed good linearity for racemic ketamine with R\(^2\) of 0.9995 for S-ketamine and 0.9994 for R-ketamine. The lowest quantifiable content of S-ketamine found in R-ketamine was 0.45%.
KW  - ketamine
KW  - capillary electrophoresis
KW  - design of experiments
KW  - cyclodextrins
KW  - enantiomers
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324713
SN  - 0009-5893
VL  - 86
IS  - 1
ER  - 
TY  - JOUR
A1  - Urlaub, Jonas
A1  - Kaiser, Reinhard P.
A1  - Scherf‐Clavel, Oliver
A1  - Bolm, Carsten
A1  - Holzgrabe, Ulrike
T1  - Investigation of isomerization of dexibuprofen in a ball mill using chiral capillary electrophoresis
JF  - Electrophoresis
N2  - Besides the racemate, the S‐enantiomer of ibuprofen (Ibu) is used for the treatment of inflammation and pain. Since the configurational stability of S‐Ibu in solid state is of interest, it was studied by means of ball milling experiments. For the evaluation of the enantiomeric composition, a chiral CE method was developed and validated according to the ICH guideline Q2(R1). The addition of Mg\(^{2+}\), Ca\(^{2+}\), or Zn\(^{2+}\) ions to the background electrolyte (BGE) was found to improve Ibu enantioresolution. Chiral separation of Ibu enantiomers was achieved on a 60.2 cm (50.0 cm effective length) x 75 μm fused‐silica capillary using a background electrolyte (BGE) composed of 50 mM sodium acetate, 10 mM magnesium acetate tetrahydrate, and 35 mM heptakis‐(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin (TM‐β‐CD) as chiral selector. The quantification of R‐Ibu in the mixture was performed using the normalization procedure. Linearity was evaluated in the range of 0.68–5.49% R‐Ibu (R\(^{2}\) = 0.999), recovery was found to range between 97 and 103%, the RSD of intra‐ and interday precision below 2.5%, and the limit of quantification for R‐ in S‐Ibu was calculated to be 0.21% (extrapolated) and 0.15% (dilution of racemic ibuprofen), respectively. Isomerization of S‐Ibu was observed under basic conditions by applying long milling times and high milling frequencies.
KW  - capillary electrophoresis
KW  - chiral separation
KW  - Ibuprofen
KW  - isomerization
KW  - validation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225852
VL  - 42
IS  - 17-18
SP  - 1790
EP  - 1799
ER  -